Maria Luisa Di Pietro

Health Technology Assessment of Belimumab: A New Monoclonal Antibody for the Treatment of Systemic Lupus Erythematosus

Objective. Systemic lupus erythematosus (SLE) is treated with anti-inflammatory and immunosuppressive drugs and off-label biologics. Belimumab is the first biologic approved after 50 years as an add-on therapy for active disease. This paper summarizes a health technology assessment performed in Italy. Methods. SLE epidemiology and burden were assessed using the best published international and national evidences and efficacy and safety of belimumab were synthesized using clinical data. A cost-effectiveness analysis was performed by a lifetime microsimulation model comparing belimumab to standard of care (SoC). Organizational and ethical implications were discussed. Results. Literature review showed that SLE affects 47 per 100,000 people for a total of 28,500 patients in Italy, 50% of whom are affected by active form of the disease despite SoC. These patients, if autoantibodies and anti-dsDNA positive with low complement, are eligible for belimumab. SLE determines work disability and a 2–5-fold increase in mortality. Belimumab with SoC may prevent 4,742 flares in three years being cost-effective with an incremental cost-effectiveness ratio of €32,859 per quality adjusted life year gained. From the organizational perspective, the development of clear and comprehensive clinical pathways is crucial. Conclusions. The assessment supports the use of belimumab into the SLE treatment paradigm in Italy.

Nutritional habits in Italian university students

INTRODUCTION Dietary habits have been indicated by research as key elements in both disease pathogenesis and prevention and health promotion. MATERIALS AND METHODS We analyzed data collected from Italian university students regarding consumption of fruits, vegetables, fast-foods, sweets, energizing drinks, and coffee, average number of eating episodes per day and regularity of breakfast habits. RESULTS 44% of the university student population eats in average at least 1 portion of fruit per day. 22.5% eats at least 2 portions of vegetables per day. 8.5% eats in average 5 times per day with 48.6% declaring an average of 3 eating episodes per day. 11.3% consumes eccessive amounts of caffeine. 49.1% of the females reaches the recommended consumption of fruit, compared to only 33.8% of males (p < 0.05). 27.7% of females eats at least 2 portions of vegetables per day, compared to 12.0% of males (p < 0.05). Eccessive coffee drinkers pass from 8.9% in the 18-21 age group to 16% in the 25-30 year old age group (p < 0.05). DISCUSSION This study showed that the eating habits of young adults do not follow national recommendations. Less than 50% of university students eats at least 1 portion of fruit per day and less than 1 out of 4 eats at least 2 portions of vegetables per day. Less than 10% of the students eats in average 5 times per day and more than 1 out of 3 does not have breakfast regularly every morning. CONCLUSION Interventions targeting university students are required in order to increase their knowledge on healthy eating habits and to ameliorate their dietary behaviours.

The Prevention of Postmenopausal Osteoporotic Fractures: Results of the Health Technology Assessment of a New Antiosteoporotic Drug

Objective. The Health Technology Assessment (HTA) approach was applied to denosumab in the prevention of osteoporotic fractures in postmenopausal women. Method. Epidemiological, clinical, technical, economic, organizational, and ethical aspects were considered. Medical electronic databases were accessed to evaluate osteoporosis epidemiology and therapeutical approaches. A budget impact and a cost-effectiveness analyses were performed to assess economic implications. Clinical benefits and patient needs were considered with respect to organizational and ethical evaluation. Results. In Italy around four millions women are affected by osteoporosis and have a higher risk for fractures with 70,000 women being hospitalized every year. Bisphosphonates and strontium ranelate are recommended as first line treatment for the prevention of osteoporotic fractures. Denosumab is effective in reducing vertebral, nonvertebral, and hip/femoral fractures with an advantage of being administered subcutaneously every six months. The budget impact analysis estimated a reduction in costs for the National Health Service with the introduction of denosumab. Furthermore, the economic analysis demonstrated that denosumab is cost-effective in comparison to oral bisphosphonates and strontium ranelate. Denosumab can be administered in outpatients by involving General Practitioners in the management. Ethical evaluation is positive because of its efficacy and compliance. Conclusion. Denosumab could add value in the prevention of osteoporotic fractures.

Heterologous assisted reproduction and kernicterus: The unlucky coincidence reveals an ethical dilemma

Secrecy and anonymity related to heterologous assisted reproduction may hide basic newborn data to neonatologists. Secrecy and anonymity are discussed in view of their possible consequences on relational dynamics and on developmental psychology. Nevertheless, they can also involve the offsprings genetic status regarding inheritable diseases. International guidelines have been recently published on this topic. Because no guidelines are ‘ideal’ unfortunate and possibly dramatic consequences can occur. We aimed to embark on a debate about this matter starting with a real clinical experience. In our case a rarely fatal but widespread disease, together with the lack of knowledge about parental status led, in a fast succession of clinical events, to the unavoidable insurgence of kernicterus.

Cryopreservation of testicular tissue in pediatrics: practical and ethical issues

Abstract The exposure to cancer treatments (chemotherapy, radiotherapy, surgery) can adversely affect all aspects of reproductive health, possibly determining temporary or permanent hypogonadism of a primary or secondary form. In prepubertal male patients, the only option for preserving fertility is testicular tissue banking. Although significant progress has been made in fertility-based animal research with SSCs, this procedure is still in an early experimental stage. Can an experimental technique, which has potential benefits and possible risks, be offered to minors? What is the minor’s best interest in this situation? Is it more important to minimize the risks of morbidity and mortality or to preserve the child’s future fertility?

Cryopreservation of ovarian tissue in pediatrics: what is the child's best interest?

In paediatric female patients the only option for restoring fertility after chemotherapy and radiotherapy is ovarian tissue banking. Even if this procedure is considered the most promising available, anyway it is still an experimental option due to the paucity of data. The possibility to offer an experimental preventive technique with potential benefits but with known risks arises a dilemma: what is the best interest for suffering child? Is it most important to minimize risk of the disease or to preserve the future fertility? However, if it is right to propose fertility preservation when physical and psychic risks are acceptable, we think it is not in the child’s best interest to retrieve ovarian tissue from very young patients whose ovaries are small and for whom surgery is a high risk procedure. Moreover fertility preservation should not be offered if this could increase the risk of disease worsening.

HTA of genetic testing for susceptibility to venous thromboembolism in Italiy

Venous thromboembolism (VTE) is a condition in which a thrombus (a solid mass of blood constituents) forms in a vein. VTE represents an extremely common medical problem manifested as either deep venous thrombosis (DVT) or pulmonary embolism (PE) affecting apparently healthy as well as hospitalized patients. Often PE is the physiopathological consequence of the DVT of low extremities vessels, in particular of the calve......

Placebo-controlled trials in pediatrics and the child’s best interest

For too long children have received medicines not sufficiently studied for their needs and, in fact, being considered as small replicas of adults, it was deemed sufficient to adjust the dosage of a drug approved for adults. Together with the limited availability of appropriate drug formulations, especially for neonates and toddlers, this approach has caused increased iatrogenic risk and/or suboptimal adherence to treatment. With the aim of encouraging the development of more efficacious and safer medicines for children, the Regulatory Agencies in Europe and U.S.A. commendably issued directives to promote adequate and well controlled pediatric clinical trials. In compliance with the agenda of the Pediatric Regulation, in the past decade the number of pediatric patients enrolled in double-blind randomized clinical trials (RCTs) is markedly increased. In order to establish the efficacy of new medicines, RCTs frequently include a placebo-control group that carries the burden of additional, and to some extent underestimated, ethical concerns with respect to trials in adults. Six years into the Pediatric Regulation implementation, off-patent drugs, most of which at present are extensively used off-label, are underrepresented in ongoing/proposed pediatric RCTs. We debate this status quo to assess what might be the child’s best interest. In fact, we argue that well-designed studies, in which efficacy and safety of new drugs are compared to off-patent drugs that are currently prescribed off-label, would achieve the aim of the Pediatric Regulation better and more ethically than placebo controlled RCTs.

Female genital mutilation of minors in Italy: is a harmless and symbolic alternative justified?

In 2004, Omar Abdulcadir - a gynecologist of the Centre for the prevention and therapy of female genital mutilation (FMG) at the Careggi Hospital (Florence) - proposed a “harmless and symbolic” alternative to FMG, which consists in the puncture of the clitoris under local anesthesia, in order to allow the outflow of some drops of blood (1). The intention behind the symbolic alternative is to avoid more severe forms of FGM while respecting cultural heritage. The proposal of this alternative procedure, which was sustained by the leaders of 10 local African immigrant communities, has encountered ample criticism (1). However, the question is: is the puncture of the clitoris prohibited by the Italian Law n. 7/2006? If it is not, could it be considered a method of reducing health risks caused by the more invasive forms of FGM (2)? Or could it culturally legitimize FGM, causing a greater difficulty in the attempts to prevent and eradicate FGM in Italy?

Methodological issues in the observational studies conducted in older population : a narrative review

Introduction: Well-conducted observational studies may represent valuable tools for getting insight to disease etiology, detecting the effect of age-related changes, and providing an important pers ...